Both T cell and B cell immune responses to HCV are being investigated. Previously we developed and characterized human monospecific antibodies to the HCV core antigen. We have now isolated and mapped similar antibodies t the structural glycoproteins E1 and E2. In collaboration with Hsu and Greenberg, we have mouse monoclonal antibodies to core, E1 and E2. These antibodies were made against recombinant baculovirus expressed proteins but have been shown to bind to the native virus itself. The antibody against E has been shown to bind HCV and thus is the first demonstration that E2 is actually a structural protein. T cell studies are continuing in an effort to identify both cytotoxic T cell and helper T cell epitopes. We are studying the proliferative response of patients with chronic HCV infections to different HCV protein antigens expressed by recombinant vaccinia virus. We are constructing a new set of eukaryotic expression clones in a sindbis virus expression system developed by Rice. These will be extremely valuabl reagents for evaluating T cell lines from patients and experimentally immunized chimpanzees.